While there is no clear consensus about the specific etiology(ies) of Parkinson's disease (PD), there is considerable recent epidemiological evidence that it is primarily an environmentally acquired disorder. From a review of current neuropathological, neurochemical and clinical evidence, the environmental factors most likely to have roles in the etiopathogenesis of PD are those which could augment endogenous oxidative stress on substantia nigra neurons through production of cytotoxic free radicals. Certain metals (i.e, iron, copper, manganese, mercury and zinc) are known to have neurochemical roles in such biochemical processes. Several of them (i.e., iron, copper, zinc and manganese) have been found in abnormal amounts in PD nigrae postmortem. Manganese is known to produce a PD-like disorder in cases with chronic exposure. One prior epidemiological study, in Singapore, has shown a significantly increased exposure history to mercury intake, as well as increased mercury blood levels in cases of PD. Our own preliminary data suggest the occurrence of an increased exposure to one or more of the metals of interest, though the means of such exposure is currently unclear. We intend to focus our proposed case-control epidemiological study on occupational exposure to, primarily, iron, copper, manganese, zinc and mercury; and secondarily, to other risk factors including a history of rural living, pesticide use, well water use and non-smoking. These last items have been suggested as risk factors in earlier analytical studies. We have developed a well-focused questionnaire to test these hypotheses. We intend to measure whole blood levels of mercury in cases and controls in order to re-examine the putative association between PD and current mercury blood level, and compare the blood level to recent exposure as assessed by the questionnaire. No prior single epidemiological study has examined exposure to all of these metals; none has included as many cases and controls, or has neurologically examined all individuals studied. None has used such a focused questionnaire. We believe that our study will add important new information to the understanding of the cause(s) of PD, a devastating, common neurological disorder.